Femoral Bone Mass Research Articles

Evaluation of Potential Roles of Zinc Finger Homeobox 3 (Zfhx3) Expressed in Chondrocytes and Osteoblasts on Skeletal Growth in Mice.

Bone formation is tightly modulated by genetically encoded molecular proteins that interact to regulate cellular differentiation and secretion of bony matrix. Many transcription factors are known to coordinate these events by controlling gene transcription within networks. However, not all factors involved are known. Here, we identified a novel function forZinc Finger Homeobox 3(Zfhx3), a gene encoding a transcription factor, as a regulator of bone metabolism. We knocked outZfhx3conditionally in mice in either chondrocytes or osteoblasts and characterized their bones by micro-CT in 12-week-old mice. We observed a negative effect in linear bone growth in both knockout mice but reduced bone mass only in mice withZfhx3deleted in osteoblasts. Loss of Zfhx3 expression in osteoblasts affected trabecular bone mass in femurs and vertebrae in both sexes but influenced cortical bone volume fraction only in females. Moreover, transcriptional analysis of femoral bones in osteoblastZfhx3conditional knockout mice revealed a reduced expression of osteoblast genes, and histological evaluation of trabecular bones suggests that Zfhx3 causes changes in bone formation and not resorption. The loss of Zfhx3 causes reductions in trabecular bone area and osteoid volume, but no changes in the expression of osteoclast differentiation markers or number of TRAP stained osteoclasts. These studies introduce Zfhx3 as a relevant factor toward understanding gene regulatory networks that control bone formation and development of peak bone mass.

Effects of unilateral nasal obstruction on mandibular condyle in mice of different ages: An exploration based on H-type angiogenesis coupling osteogenesis.

Nasal obstruction leads to a hypoxia condition throughout the entire body. In this study, the unilateral nasal obstruction (UNO) mouse model was established by blocking the left nostril of mice. The aim of this study was to investigate the effects of UNO-induced hypoxia on mandibular condyle in juvenile (3-week-old), adolescent (6-week-old) and adult (12-week-old) male C57BL/6J mice from the perspective of H-type angiogenesis coupling osteogenesis. Firstly, UNO exerted a significant inhibitory effect on weight gain in mice of all ages. However, only in adolescent mice did UNO have an obvious detrimental effect on femoral bone mass accrual. Subsequently, micro-computed tomography (CT) analysis of mandibular condylar bone mass revealed that UNO significantly retarded condylar head volume gain but increased condylar head trabecular number (Tb.N) in juvenile and adolescent mice. Furthermore, UNO promoted the ratio of proliferative layer to cartilage layer in condylar cartilage and facilitated the chondrocyte-to-osteoblast transformation in juvenile and adolescent mice. Moreover, although UNO enhanced the positive expression of hypoxia-inducible factor (HIF)-1α in the condylar subchondral bone of mice in all ages, an increase in H-type vessels and Osterix+ cells was only detected in juvenile and adolescent mice. In summary, on the one hand, in terms of condylar morphology, UNO has a negative effect on condylar growth, hindering the increase in condylar head volume in juvenile and adolescent mice. However, on the other hand, in terms of condylar microstructure, UNO has a positive effect on condylar osteogenesis, promoting the increase of condylar Tb.N, chondrocyte-to-osteoblast transformation, HIF-1α expression, H-type angiogenesis and Osterix+ cells in juvenile and adolescent mice. Although the changes in condylar morphology and microstructure caused by UNO have not yet been fully elucidated, these findings improve our current understanding of the effects of UNO on condylar bone homeostasis.

The influence of body fat content and distribution on bone mass in healthy Chinese adults.

Previous studies have reported a close relationship between body mass index (BMI) and bone mineral density (BMD). However, the effects of fat on bone mass remain controversial, particularly for fat tissue distribution. The aim of this study was to evaluate the association between regional fat percentage and BMD using a population-based database. This study included participants who were referred to the Department of Radio Diagnosis for dual-energy X-ray absorptiometry (DEXA) scan from January 2018 to December 2020. The relationships between BMI and regional fat percentage with BMD were assessed using multiple linear regression and generalized additive models. The risk of low bone mass was determined using logistic regression. There was a negative relationship between the regional fat percentage and femoral neck BMD (FN BMD) or lumbar spine BMD (LS BMD) in both genders (p < 0.05). In females, an inverted U-shaped relationship was observed between regional fat percentage and BMD at both the femoral neck and lumbar spine. The impact of trunk fat percentage on LS BMD was associated with the highest OR of low bone mass in females (OR 3.1, 95% CI 2.6 to 3.7, p for trend <0.001), while the impact of abdomen fat percentage on FN BMD was associated with the highest OR of low bone mass in males (OR 2.2, 95% CI 1.8 to 2.7, p for trend <0.001). There was an inverted U-shaped relationship between regional fat percentage and BMD. Excessive regional fat percentage may be harmful to bone health in both genders. To promote bone health, males should restrict their abdomen circumference and avoid abdominal adiposity, while females should control their trunk circumference.

Exploration of the miR-187-3p/CNR2 pathway in modulating osteoblast differentiation and treating postmenopausal osteoporosis through mechanical stress.

This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR-187-3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8-week treadmill exercise. Post-training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro-CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR-187-3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR-187-3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both invivo and invitro experiments have confirmed that mechanical stress downregulates miR-187-3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR-187-3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.

A Novel MRI-Based Paravertebral Muscle Quality (PVMQ) Score for Evaluating Muscle Quality and Bone Quality: A Comparative Study with the VBQ Score.

This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality. PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores' effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF. In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718). The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.

Hem1 is essential for ruffled border formation in osteoclasts and efficient bone resorption

Bone resorption is highly dependent on the dynamic rearrangement of the osteoclast actin cytoskeleton to allow formation of actin rings and a functional ruffled border. Hem1 is a hematopoietic-specific subunit of the WAVE-complex which regulates actin polymerization and is crucial for lamellipodia formation in hematopoietic cell types. However, its role in osteoclast differentiation and function is still unknown. Here, we show that although the absence of Hem1 promotes osteoclastogenesis, the ability of Hem1-/- osteoclasts to degrade bone was severely impaired. Global as well as osteoclast-specific deletion of Hem1 in vivo revealed increased femoral trabecular bone mass despite elevated numbers of osteoclasts in vivo. We found that the resorption defect derived from the morphological distortion of the actin-rich sealing zone and ruffled border deformation in Hem1-deficient osteoclasts leading to impaired vesicle transport and increased intracellular acidification. Collectively, our data identify Hem1 as a yet unknown key player in bone remodeling by regulating ruffled border formation and consequently the resorptive capacity of osteoclasts.

A Controlled Variable Study of the Biomechanical Properties of the Proximal Femur before and after Cancellous Bone Removal.

The biomechanical characteristics of proximal femoral trabeculae are closely related to the occurrence and treatment of proximal femoral fractures. Therefore, it is of great significance to study its biomechanical effects of cancellous bone in the proximal femur. This study examines the biomechanical effects of the cancellous bone in the proximal femur using a controlled variable method, which provide a foundation for further research into the mechanical properties of the proximal femur. Seventeen proximal femoral specimens were selected to scan by quantitative computed tomography (QCT), and the gray values of nine regions were measure to evaluated bone mineral density (BMD) using Mimics software. Then, an intact femur was fixed simulating unilateral standing position. Vertical compression experiments were then performed again after removing cancellous bone in the femoral head, femoral neck, and intertrochanteric region, and data were recorded. According to the controlled variable method, the femoral head, femoral neck, and intertrochanteric trabeculae were sequentially removed based on the axial loading of the intact femur, and the displacement and strain changes of the femur samples under axial loading were recorded. Gom software was used to measure and record displacement and strain maps of the femoral surface. There was a statistically significant difference in anteroposterior displacement of cancellous bone destruction in the proximal femur (p < 0.001). Proximal femoral bone mass explained 77.5% of the strength variation, in addition proximal femoral strength was mainly affected by bone mass at the level of the upper outer, lower inner, lower greater trochanter, and lesser trochanter of the femoral head. The normal stress conduction of the proximal femur was destroyed after removing cancellous bone, the stress was concentrated in the femoral head and lateral femoral neck, and the femoral head showed a tendency to subside after destroying cancellous bone. The trabecular removal significantly altered the strain distribution and biomechanical strength of the proximal femur, demonstrating an important role in supporting and transforming bending moment under the vertical load. In addition, the strength of the proximal femur mainly depends on the bone density of the femoral head and intertrochanteric region.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal–regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes. A reduction in distal femur bone mass was achieved after 3 weeks of hindlimb unloading in mice, which was subsequently reversed by intraperitoneal IGU treatment (30 mg/kg; five times per week). Histology revealed that hindlimb-unloaded (HLU) mice had significantly increased osteoclast number and sclerostin-positive osteocyte rates, which were suppressed by IGU treatment. Moreover, HLU mice exhibited a significant decrease in osteocalcin-positive cells, which was attenuated by IGU treatment. In vitro, IGU suppressed the gene expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in MLO-Y4 and Saos-2 cells, which inhibited osteoclast differentiation of mouse bone marrow cells in cocultures. Although IGU did not affect the nuclear translocation or transcriptional activity of NF-κB, RNA sequencing revealed that IGU downregulated the expression of early growth response protein 1 (EGR1) in osteocytes. HLU mice showed significantly increased EGR1- and tumor necrosis factor alpha (TNFα)-positive osteocyte rates, which were decreased by IGU treatment. EGR1 overexpression enhanced the gene expression of TNFα, RANKL, and sclerostin in osteocytes, which was suppressed by IGU. Contrarily, small interfering RNA-mediated suppression of EGR1 downregulated RANKL and sclerostin gene expression. These findings indicate that IGU inhibits the expression of EGR1, which may downregulate TNFα and consequently RANKL and sclerostin in osteocytes. These mechanisms suggest that IGU could potentially be used as a treatment option for disuse osteoporosis by targeting osteocytes.

Planar catechin increases bone mass by regulating differentiation of osteoclasts in mice

ObjectivesWhile catechins have been reported to exhibit potential to benefit osteoporosis patients, the effects of planar catechin (PCat), synthesized during the development of drugs for Alzheimer's disease, have not been clearly elucidated. Here, we examined the effects of PCat on mouse bone metabolism both in vivo and in vitro. MethodsSix week old female mice were orally administered PCat (30 mg/kg) every other day for four weeks, and their femurs were analyzed using micro-computed tomography imaging. Osteoclasts and osteoblasts were collected from mice and cultured with PCat. Subsequently, osteoclast formation and differentiation and osteoblast differentiation were observed. ResultsMice orally administered PCat displayed significantly increased femur bone mass compared to the control group. Quantitative polymerase chain reaction findings indicated that PCat addition to osteoclast progenitor cultures suppressed osteoclast formation and decreased osteoclast marker expression without affecting the proliferative potential of the osteoclast progenitor cells. Addition of PCat to osteoblast cultures increased osteoblast marker expression. ConclusionsPCat inhibits osteoclast differentiation and promotes osteoblast differentiation, resulting in increased bone mass in mice. These results suggest that PCat administration is a promising treatment option for conditions associated with bone loss, including osteoporosis.

Bub1 suppresses inflammatory arthritis-associated bone loss in mice through inhibition of TNFα-mediated osteoclastogenesis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovitis, bone and cartilage destruction, and increased fracture risk with bone loss. Although disease-modifying antirheumatic drugs have dramatically improved clinical outcomes, these therapies are not universally effective in all patients because of the heterogeneity of RA pathogenesis. Therefore, it is necessary to elucidate the molecular mechanisms underlying RA pathogenesis, including associated bone loss, in order to identify novel therapeutic targets. In this study, we found that Budding uninhibited by benzimidazoles 1 (BUB1) was highly expressed in RA patients' synovium and murine ankle tissue with arthritis. As CD45+CD11b+ myeloid cells are a Bub1 highly expressing population among synovial cells in mice, myeloid cell-specific Bub1 conditional knockout (Bub1ΔLysM) mice were generated. Bub1ΔLysM mice exhibited reduced femoral bone mineral density when compared with control (Ctrl) mice under K/BxN serum-transfer arthritis, with no significant differences in joint inflammation or bone erosion based on a semi-quantitative erosion score and histological analysis. Bone histomorphometry revealed that femoral bone mass of Bub1ΔLysM under arthritis was reduced by increased osteoclastic bone resorption. RNA-seq and subsequent Gene Set Enrichment Analysis demonstrated a significantly enriched nuclear factor-kappa B pathway among upregulated genes in receptor activator of nuclear factor kappa B ligand (RANKL)-stimulated bone marrow-derived macrophages (BMMs) obtained from Bub1ΔLysM mice. Indeed, osteoclastogenesis using BMMs derived from Bub1ΔLysM was enhanced by RANKL and tumor necrosis factor-α or RANKL and IL-1β treatment compared with Ctrl. Finally, osteoclastogenesis was increased by Bub1 inhibitor BAY1816032 treatment in BMMs derived from wildtype mice. These data suggest that Bub1 expressed in macrophages plays a protective role against inflammatory arthritis-associated bone loss through inhibition of inflammation-mediated osteoclastogenesis.

Applying Machine Learning Analysis Based on Proximal Femur of Abdominal Computed Tomography to Screen for Abnormal Bone Mass in Femur

To evaluate the performance of machine learninganalysis based on proximal femur of abdominal computed tomography (CT) scans in screening for abnormal bone mass in femur. 222 patients aged 50 years or older who underwent abdominal CT and dual-energy X-ray absorptiometryscans within 14 dayswere retrospectively enrolled. The patients were randomly assigned to a training cohort (n=155) and a testing cohort (n=67) in a ratio of 7:3. A total of 2288 candidate radiomic features were extracted from the volume region of interest- the left proximal femur of the abdominal CT scans. The most valuable radiomic features were selected using minimum-Redundancy Maximum-Relevancyand the least absolute shrinkage and selection operatorto construct the radiomics model. The predictive performance was assessed with receiver operating characteristiccurve. 13 features were chosen to establish the radiomics model. The radiomics model using logistic regressiondisplayed excellent prediction performance in distinguishing normal bone mass and abnormal bone mass, with the area under the curve (AUC), accuracy, sensitivity and specificity of 0.917 (95% CI, 0.867-0.967), 0.826, 0.935 and 0.780 in the training cohort. The testing cohort indicated a better performance with AUC, accuracy, sensitivity and specificity of 0.963 (95% CI, 0.919-0.999), 0.851, 0.923 and 0.889. The radiomics model based on proximal femur of abdominal CT scans had a high predictive performance to identify abnormal bone mass in femur, which can be used as a tool for opportunistic osteoporosis screening.

Exercise training modifies the bone and endocrine response to graded reductions in energy availability in skeletally mature female rodents.

Reductions in energy availability leading to weight loss can induce loss of bone and impact important endocrine regulators of bone integrity. We sought to elucidate whether endurance exercise (EX) can mitigate bone loss observed in sedentary (SED) skeletally mature rodents subjected to graded energy deficits. Female virgin rats (n=84, 5-mo-old; 12/group) were randomized to baseline controls and either sedentary (SED) or exercise (EX) conditions, and within each exercise status to adlib-fed (ADLIB), or moderate (MOD) or severe (SEV) energy restriction diets for 12 weeks. Rats assigned to EX groups performed treadmill running to increase weekly energy expenditure by 10%. MOD-ER-SED, SEV-ER-SED, MOD-ER-EX and SEV-ER-EX were fed modified AIN93M diets with 20%, 40% 10%, and 30% less energy content, respectively, with 100% of all other nutrients provided. Energy availability (EA) was effectively reduced by ~14% and ~30% in the MOD-ER and SEV-ER groups, respectively. MOD-ER for 12 weeks resulted in few negative impacts on bone and, except for serum leptin in MOD-ER-SED rats, no significant changes in endocrine factors. By contrast, SEV-ER in SED rats resulted in significantly lower total body and femoral neck bone mass, and reduced serum estradiol, IGF-1 and leptin. EX rats experiencing the same reduction in energy availability as SEV-ER-SED exhibited higher total body mass, lean mass, total BMC, and higher serum IGF-1 at the end of 12 weeks. Bone mechanical properties at 3 bone sites (mid-femur, distal femur, femoral neck) were minimally impacted by ER but positively affected by EX. These findings indicate that combining increased EX energy expenditure with smaller reductions in energy intake to achieve a targeted reduction in EA provides some protection against loss of bone mass and lean mass in skeletally mature female rats, likely due to better preservation of circulating IGF-1, and that bone mechanical integrity is not significantly degraded with either moderate or severe reduced EA.

DNA damage-inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models.

Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage-inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis in femur. However, the role of DDIT3 in periodontitis has not been elucidated. This research aimed to explore the role and mechanisms of DDIT3 in periodontitis. DDIT3 gene knockout (KO) mice were generated using a CRISPR/Cas9 system. Experimental periodontitis models were established to explore the role of DDIT3 in periodontitis. The expression of DDIT3 in periodontal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The alveolar bone phenotypes were observed by micro-CT and stereomicroscopy. The inflammation levels and osteoclast activity were examined by histological staining, immunostaining, and qRT-PCR. Bone marrow-derived macrophages (BMMs) were isolated to confirm the effects of DDIT3 on osteoclast formation and function in vitro. The increased expression of DDIT3 in murine inflamed periodontal tissues was detected. DDIT3 knockout aggravated alveolar bone loss and enhanced expression levels of inflammatory cytokines in murine periodontitis models. Increased osteoclast formation and higher expression levels of osteoclast-specific markers were observed in the inflamed periodontal tissues of KO mice. In vitro, DDIT3 deficiency promoted the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts and the bone resorption activity of mature osteoclasts. Our results demonstrate that DDIT3 deletion aggravated alveolar bone loss in experimental periodontitis through enhanced inflammatory reactions and osteoclastogenesis. The anti-inflammation and the inhibition of bone loss by DDIT3 in murine periodontitis provides a potential novel therapeutic strategy for periodontitis.

Fragile X Messenger Ribonucleoprotein 1 (FMR1), a novel inhibitor of osteoblast/osteocyte differentiation, regulates bone formation, mass, and strength in young and aged male and female mice

Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene mutations lead to fragile X syndrome, cognitive disorders, and, in some individuals, scoliosis and craniofacial abnormalities. Four-month-old (mo) male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass. However, consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown. We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2- and 9-mo mice. The cancellous bone mass is higher only in females, whereas, cortical bone mass is higher in 2- and 9-mo males, but higher in 2- and lower in 9-mo female FMR1-knockout mice. Furthermore, male bones show higher biomechanical properties at 2mo, and females at both ages. Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro, without affecting osteoclasts in vivo/ex vivo. Thus, FMR1 is a novel osteoblast/osteocyte differentiation inhibitor, and its absence leads to age-, site- and sex-dependent higher bone mass/strength.

Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone.

Colony-stimulating factor 1 (Csf1) is an essential growth factor for osteoclast progenitors and an important regulator for bone resorption. It remains elusive which mesenchymal cells synthesize Csf1 to stimulate osteoclastogenesis. We recently identified a novel mesenchymal cell population, marrow adipogenic lineage precursors (MALPs), in bone. Compared to other mesenchymal subpopulations, MALPs expressed Csf1 at a much higher level and this expression was further increased during aging. To investigate its role, we constructed MALP-deficient Csf1 CKO mice using AdipoqCre. These mice had increased femoral trabecular bone mass, but their cortical bone appeared normal. In comparison, depletion of Csf1 in the entire mesenchymal lineage using Prrx1Cre led to a more striking high bone mass phenotype, suggesting that additional mesenchymal subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts in the femoral secondary spongiosa region of Csf1 CKOAdipoq mice, but not at the chondral-osseous junction nor at the endosteal surface of cortical bone. Moreover, Csf1 CKOAdipoq mice were resistant to LPS-induced calvarial osteolysis. Bone marrow cellularity, hematopoietic progenitors, and macrophages were also reduced in these mice. Taken together, our studies demonstrate that MALPs synthesize Csf1 to control bone remodeling and hematopoiesis.

Bone Remodelling of the Proximal Femur After Hip Revision with a Metaphyseal-Fixation Femoral Stem Component.

Whether hip revision with a metaphyseal-fixation femoral stem component can restore the bone mass of the proximal femur remains unclear. The aims of this study were to identify whether the bone mineral density (BMD) of the proximal femur increases following hip revision with a metaphyseal-fixation femoral stem and to identify the factors associated with BMD recovery. This was a retrospective study involving 36 patients who underwent hip arthroplasty with a metaphyseal-diaphyseal fixation stem (standard length stem) and had indications for hip revision, which was performed with a proximal press-fit short-stem prosthesis for each patient. Dual-energy X-ray absorptiometry (DEXA) was used to obtain, evaluate, and compare the BMD at baseline and one year and two years postoperatively. The proximal femur was divided into several independent areas according to the Gruen zone (Gruen 1 to Gruen 7 from the greater trochanter counterclockwise to the lesser trochanter). Logistic regression analyses were used to assess potential factors significantly associated with an increase in BMD. An increased BMD was obviously identified in the proximal femur. Two years after the surgery, the BMD of the Gruen 1, Gruen 2, Gruen 6, and Gruen 7 areas had increased by 22.6%, 12.6%, 16.2% and 24.2%, respectively, relative to baseline. Three independent risk factors associated with bone mineral density recovery were identified: age (OR=1.100, 95% CI=1.005-1.203, P=0.038), osteoporosis (OR=14.921, 95% CI=1.223-182.101, P=0.034) and fair to poor hip function (OR=13.142, 95% CI=1.024-168.582, P=0.048). This study confirms that metaphyseal-fixation stem hip revision can indeed help restore bone mass in the proximal femur, especially in the Gruen 1, Gruen 2, Gruen 6 and Gruen 7 zones. It was also found that advanced age, osteoporosis, and fair to poor hip joint function were three important risk factors affecting the recovery of proximal femur bone mass after surgery. Retrospectively registered.

POL-RISK: an algorithm for 10-year fracture risk prediction in postmenopausal women from the RAC-OST-POL study.

Fragility fractures are the major consequence of osteoporosis. Thus, fracture risk assessment is an essential part of the diagnostic process in osteoporosis. The aim of the study was to develop an algorithm for fracture risk prediction. Bone status was evaluated in a population‑basedcohort of postmenopausal women at a mean (SD) age of 66.4 (7.8) years. Subsequently, all participants were contacted by phone once a year (for 10 consecutive years) to update their history of fractures. At the end of the 10‑year follow‑up, the number of the study participants was 640, of whom 129 had a history of 190 osteoporotic fractures recorded during the study period. Statistical analysis included multistep data preprocessing, feature selection, identification of fracture risk factors, and design of the final model. Logistic regression models were fitted and used for the evaluation of variables from determined feature sets, including global fit measures, as well as individual parameters, such as the Wald statistic and P value, odds ratio, and 95% CI. The 10‑year risk for any fracture depended on the age of the patient, the number of recorded fractures after the age of 40 years, femoral neck bone mass, and the occurrence of falls during the previous year. The achieved equation was incorporated into an algorithm, available at the www.fracture‑risk.pl webpage. A fracture prediction algorithm was developed in a longitudinal study to enable calculation of the 10‑year fracture risk. Identification of patients at a high risk of fracture should be followed by implementation of appropriate treatment strategy to reduce the number of future fractures.

Changes in adipose bone marrow and bone morphology in X-linked hypophosphatemic rickets

IntroductionX-linked hypophosphatemic (XLH) rickets causes significant bone deformities in the lower limbs resulting from a bone mineralization defect. According to Frost's Mechanostat theory, compensatory modeling of the bones takes place during increased mechanical loads. In addition, mechanical stimuli modulate the differentiation of mesenchymal stem cells; common precursors to bone marrow adipocytes and osteoblasts. HypothesisBone deformities of the lower limbs lead to increased femoral bone mass and decreased fatty infiltration of the bone marrow (FIBM) in children with XLH rickets compared to a control group. Patients and methodsEleven children (10.3years [6–17]) with XLH rickets and 22 healthy children (10.2years [5–15.5]) underwent lower limb Magnetic Resonance Imaging. A calculation of FIBM was performed at the mid-femur, as well as a calculation of the total bone cross-sectional area (CSA), the cortical CSA, the anteroposterior and mediolateral axes of the femur, bone marrow and the thickness of the femoral cortices. ResultsTotal bone CSA, total cortical CSA and bone marrow CSA were higher in the XLH group than in the control group (p<0.05). The mid-lateral diameters of the femur and bone marrow were more elongated than those of the control group (p<0.001). Only the anterior cortex was thinned in the XLH group (p=0.001), while there was no difference with the control group for the posterior, medial and lateral cortices. The total percentage of FIBM was 72.81% [±3.95] and 77.4% [±5.52] for the XLH and control groups respectively (p<0.001). DiscussionThe increase in bone mass in the XLH population reflects an adaptation of bone tissue to the bone deformities present in this pathology. The decrease in FIBM indicates a lower risk of osteoporosis in the XLH population and may constitute a new monitoring parameter in this pathology. Level of studyIII; Case-control study.

The effects on type 2 diabetes mellitus mouse femoral bone achieved by anti-osteoporosis exercise interventions.

Exercise therapy and key regulators of bone quality exert anti-hyperglycemic effects on type 2 diabetes mellitus (T2DM) mice. A number of programs have been reported to have an effect on bone disease in T2DM. Major unanswered questions concern the potential correlation of exercise with the improvement of bone quality in T2DM mice and how the nonlinear optical properties of bone are correlated with changes to its crystal structure. Subjects were randomly divided into six groups: 1) control (C) group, which was fed a normal diet (n=8); 2) T2DM quiet group, which was given a high-fat diet and quiet (n=8); 3) T2DM plus swimming (T2DM+S) group, which received T2DM and swim training (n=8); 4) T2DM plus resistance exercise (T2DM+RE) group, which was given T2DM and resistance exercise (n=8); 5) T2DM plus aerobic exercise (T2DM+AE) group, with T2DM and medium-intensity treadmill exercise (n=8); and 6) T2DM plus high-intensity interval training (T2DM+HIIT), with T2DM and high-intensity variable-speed intervention (n=8). The levels of runt-related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase (ALP), as well as the bone microstructure and morphometry, were measured at the end of the 8-week exercise intervention. Compared with the C group, the bone microstructure indexes [bone mineral density (BMD), bone volume/tissue volume (BV/TV), cortical thickness (Ct.Th), and connectivity density (Conn.D)], the bone biomechanical properties (maximum load, fracture load, yield stress, and elastic modulus), and the osteogenic differentiation factors (RUNX2, OSX, and BMP2) of the T2DM group were significantly decreased (all p<0.05). Compared with the T2DM group, there were obvious improvements in the osteogenic differentiation factor (OSX) and Th.N, while the separation of trabecular bone (Tb.Sp) decreased in the T2DM+AE and T2DM+HIIT groups (all p<0.05). In addition, the bone microstructure indicators BV/TV, tissue mineral density (TMD), Conn.D, and degree of anisotropy (DA) also increased in the T2DM+HIIT group, but the yield stress and Ct.Th deteriorated compared with the T2DM group (all p<0.05). Compared with the T2DM+S and T2DM+RE groups, the BV/TV, trabecular number (Tb.N), Tb.Sp, and Conn.D in the T2DM+AE and T2DM+HIIT groups were significantly improved, but no significant changes in the above indicators were found between the T2DM+S and T2DM+RE groups (all p<0.05). In addition, the BMD and the expression of ALP in the T2DM+AE group were significantly higher than those in the T2DM+HIIT group (all p<0.05). There was a significant deterioration in femur bone mass, trabecular bone microarchitecture, cortical bone geometry, and bone mechanical strength in diabetic mice. However, such deterioration was obviously attenuated in diabetic mice given aerobic and high-intensity interval training, which would be induced mainly by suppressing the development of T2DM. Regular physical exercise may be an effective strategy for the prevention of not only the development of diabetes but also the deterioration of bone properties in patients with chronic T2DM.

RF06 | PSAT152 Associations between Bone Mass, Hormone Levels and Body Composition in Postmenopausal Women

Abstract Emerging evidence suggests an association between FSH and bone mass in peri- and postmenopausal women. The aim of the present study was to assess body composition parameters and hormone levels as risk factors for low bone mass in women with recent menopause. In this cross-sectional study, we analyzed biorepository samples from 139 postmenopausal women aged 42 to 68 years with no evidence of clinical CVD. Inclusion criteria were as follows: menopause, defined as last menstrual period at least 12 months of amenorrhea and/or 6 months or more of amenorrhea plus FSH levels ≥35 mIU/mL occurring after 40 years of age, and no use of hormone therapy (HT) in the past 3 month. BMD and body composition were assessed by dual-energy X-ray absorptiometry (DXA), SHBG and FSH levels were measured in all patients. Serum estradiol levels were measured by gas chromatography/tandem mass spectrometry assay (GC/MS/MS) in a subset of 57 participants and free estrogen index (FEI) was estimated by dividing estradiol by SHBG × 100. Low bone mass was considered osteoporosis and osteopenia. The mean age was 54.33±5.30 years and median time since menopause was 4 (2 - 9) years. The mean BMI was 26.73±4.38 kg/m2 and 66% of participants were classified as overweight or obese. BMI, BMD and T-sc, lean mass index (LMI) and fat mass index (FMI) were lower, and SHBG was higher in women with FSH levels above the median values (83.6mUI/mL). FSH was inversely correlated with FEI (rho=-0.283, p=0.033) as well as with FMI (rho=-0.288, p=0.001) and LMI (rho=-0.186, p=0.029), but significance was lost after adjustment for estradiol levels (p=0.651). In the univariate linear regression analysis, FSH, FEI, time since menopause, SHBG, FMI and LMI were significant predictors to total femur bone mass, explaining 3.8%, 11.9%, 7.4%, 14.7%, 19.7% and 8.4% of variance in BMD at this site, respectively. In the multivariate model, the association of FSH, time since menopause and FMI with hip bone mass was no longer significant after inclusion of FEI in the respective model. The present results indicate that the negative association between FSH levels and femoral BMD in postmenopausal women are influenced by endogenous estradiol levels, time since menopause and fat mass. Additional studies are needed in order to further analyze whether some direct effect of FSH on bone mass may be additive to the presence of low bone mass in this population. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.